TR&D 4 Spatial Modeling: Modeling Framework for Cell Motility Project Summary Modeling and simulation of cell motility is an exciting new direction, which expands beyond biochemistry and electrophysiology to incorporate mechano-chemical processes and mechanical properties of cellular structures. This project extends VCell to develop an integrated modeling and data processing environment for cell shape changes driven by mechanical forces. It directly supports the numerical methods for cell kinematics and cell mechanics developed in TR&D2. Many of the capabilities we introduce will enhance all spatial modeling, including static geometries. In Aim 1 we develop a framework to create kinematic models of moving and/or deforming cells, using anatomical landmarks and local cell coordinates to describe subcellular localization of regions of interest and spatial functions. This aim creates the computational infrastructure for solution of reaction-diffusion-advection problems within changing geometries. Driving Biomedical Projects from the Haugh and Wu laboratory drive the need to create VCell BioModels of signaling pathways within migrating cells. In Aim 2 we will create a framework for describing mechano-chemical processes as components of VCell models, responding to the DBPs by Mogilner, Pollard and Inoue. The resulting forces will result in kinematics that are treated in Aim 1. The analysis of simulation results and the use of experimental data to constrain models and/or validate model predictions pose new challenges when cells move and change shape. Therefore, in Aim 3 we will build an integrated suite of tools for analyzing and comparing simulation results and experimental data in the context of cell motion; this will also be useful across all spatial modeling applications in VCell, including any optogenetic or dynamic fluorescence microscopy experiments.